The role of p75NTR in inducing axonal degeneration after injury

MONTROULL, LAURA; FRIEDMAN, WILMA J.

Congreso; ASN Meeting 2018; 2018

Expression of p75NTR is induced in numerous Central Nervous System (CNS) neurons after damage in the adult brain and has been shown to regulate neuronal cell death in several injury models. We have previously demonstrated that blocking either p75NTR or its ligands can attenuate neuronal death in a severe model of traumatic brain injury (TBI). While the neuropathological consequences of TBI are heterogeneous, diffuse axonal injury is ubiquitous at all severity levels, leading to deficits in connectivity that may or may not recover over time. The molecular mechanisms that regulate axonal degeneration after TBI are just beginning to be understood. p75NTR has been widely studied in the Peripheral Nervous System in various injury and cell-death paradigms, as well as in axonal pruning and degeneration. However, the role of this receptor in mediating axonal degeneration after TBI in the adult CNS remains unclear. To determine the role of p75NTR in this process we performed in vivo and in vitro experiments. We subjected adult mice to mild traumatic injury using lateral fluid percussion brain (LFP) injury model. We found that one day after LFP, p75NTR is upregulated in axons and this increase is maintained 3 days after the injury. The colocalization of p75NTR with the marker for axonal damage, βAPP, suggest that those axons are degenerating. To understand the mechanisms of p75NTR in mediating axonal degeneration, and determining whether this is independent or part of a continuum leading to neuronal death, we are using a variety of in vitro approaches including an in vitro model of axonal stretch injury and microfluidic chambers to examine axon-specific signaling mechanisms